期刊
ACS SYNTHETIC BIOLOGY
卷 4, 期 6, 页码 682-688出版社
AMER CHEMICAL SOC
DOI: 10.1021/sb5003218
关键词
combinatorial engineering; bisindole biosynthesis; glycosyltransferase; halogenase; flavin-dependent monooxygenase; synthetic pathways
资金
- Canadian Institutes of Health Research
- Genome British Columbia
- Michael Smith Foundation for Health Research Fellowship
Cladoniamides are indolotryptoline natural products that derive from indolocarbazole precursors. Here, we present a microbial platform to artificially redirect the cladoniamide pathway to generate unnatural bisindoles for drug discovery. Specifically, we target glycosyltransferase, halogenase, and oxidoreductase genes from the phylogenetically related indolocarbazole rebeccamycin and staurosporine pathways. We generate a series of novel compounds, reveal details about the substrate specificities of a number of enzymes, and set the stage for future efforts to develop new catalysts and compounds by engineering of bisindole genes. The strategy for structural diversification we use here could furthermore be applied to other natural product families with known biosynthetic genes.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据